crossing96/oncoscreening huggingface dataset:
Unrecognised paraganglioma of the urinary bladder precipitating hypertensive crisis.	Bladder paragangliomas (bPGLs) account for only 0.06% of all bladder tumours, most commonly presenting with post-micturition syncope and hypertensive crisis. Silent paragangliomas are very rare, and failure to recognise them in the perioperative setting can precipitate a hypertensive crisis in the absence of sufficient alpha-blockade. Here, we describe a case of unrecognised bPGL in a woman with pre-existing hypertension and a single prior episode of haematuria thought to be related to urothelial carcinoma. She was found to have a low-grade non-invasive papillary urothelial carcinoma (potentially the cause of her haematuria) and an unrelated vascular-appearing tumour causing hypertensive crisis and broad complex tachycardia on resection. This was confirmed to be a bPGL on histology for which she underwent definitive management with a partial cystectomy following blood pressure management.	bladder
[Practical application of the Paris system for reporting urinary cytology].	Objective: To validate the diagnostic performance of the Paris system for reporting urinary cytology (TPS). Methods: A total of 7 046 urine cytology samples from 3 402 patients collected in the Department of Pathology, Beijing Hospital, China from January 2020 to January 2022 were analyzed. 488 patients had a biopsy or resection specimen during the follow-up period of 6 months. The sensitivity, specificity, risk of malignancy (ROM) and risk of high-grade malignancy (ROHM) of the TPS were evaluated using histological diagnosis as the golden standard. Results: Among the 7 046 samples, high-grade urothelial carcinoma (HGUC) accounted for 5.7% (399/7 046), suspicious for high-grade urothelial carcinoma (SHGUC) for 3.2% (227/7 046), atypical urothelial cells (AUC) for 8.4% (593/7 046), and negative for high-grade urothelial carcinoma (NHGUC) for 72.9% (5 139/7 046) including low-grade urothelial neoplasm (LGUN) for 0.8% (59/7 046) and insufficient samples for 9.8% (688/7 046). 488 patients had a bladder biopsy or resection in the follow-up of six months, including 314 males and 174 females, aged 27 to 92 years (average, 66 years). The ROHM of TPS was 94.7% in HGUC, 83.3% in SHGUC, 41.3% in AUC and 18.8% in NHGUC. The sensitivity and specificity of urine cytology were 70.1% (169/241) and 97.0% (162/167), respectively. The negative predictive value of NHGUC was 69.2% (162/234). Conclusions: The study has shown that TPS classification has high sensitivity and specificity, high ROHM for HGUC and SHGUC, and high negative predictive value for NHGUC. The application of TPS reporting system can better interpret the clinical significance of cytology samples, improve the accuracy of urine cytopathology and ensure continuous diagnostic consistency.	bladder
Predicting preoperative muscle invasion status for bladder cancer using computed tomography-based radiomics nomogram.	OBJECTIVES: The aim of the study is to assess the efficacy of the established computed tomography (CT)-based radiomics nomogram combined with radiomics and clinical features for predicting muscle invasion status in bladder cancer (BCa). METHODS: A retrospective analysis was conducted using data from patients who underwent CT urography at our institution between May 2018 and April 2023 with urothelial carcinoma of the bladder confirmed by postoperative histology. There were 196 patients enrolled in all, and each was randomized at random to either the training cohort (n = 137) or the test cohort (n = 59). Eight hundred fifty-one radiomics features in all were retrieved. For feature selection, the significance test and least absolute shrinkage and selection operator (LASSO) approaches were utilized. Subsequently, the radiomics score (Radscore) was obtained by applying linear weighting based on the selected features. The clinical and radiomics model, as well as radiomics-clinical nomogram were all established using logistic regression. Three models were evaluated using analysis of the receiver operating characteristic curve. An area under the curve (AUC) and 95% confidence intervals (CI) as well as specificity, sensitivity, accuracy, negative predictive value, and positive predictive value were included in the analysis. Radiomics-clinical nomogram's performance was assessed based on discrimination, calibration, and clinical utility. RESULTS: After obtaining 851 radiomics features, 12 features were ultimately selected. Histopathological grading and tortuous blood vessels were included in the clinical model. The Radscore and clinical histopathology grading were among the final predictors in the unique nomogram. The three models had an AUC of 0.811 (95% CI, 0.742-0.880), 0.845 (95% CI, 0.781-0.908), and 0.896 (95% CI, 0.846-0.947) in the training cohort and in the test cohort they were 0.808 (95% CI, 0.703-0.913), 0.847 (95% CI, 0.739-0.954), and 0.887 (95% CI, 0.803-0.971). According to the DeLong test, the radiomics-clinical nomogram's AUC in the training cohort substantially differed from that of the clinical model (AUC: 0.896 versus 0.845, p = 0.015) and the radiomics model (AUC: 0.896 versus 0.811, p = 0.002). The Delong test in the test cohort revealed no significant difference among the three models. CONCLUSIONS: CT-based radiomics-clinical nomogram can be a useful tool for quantitatively predicting the status of muscle invasion in BCa.	bladder
Loss of LPAR6 and CAB39L dysregulates the basal-to-luminal urothelial differentiation program, contributing to bladder carcinogenesis.	"We describe a strategy that combines histologic and molecular mapping that permits interrogation of the chronology of changes associated with cancer development on a whole-organ scale. Using this approach, we present the sequence of alterations around RB1 in the development of bladder cancer. We show that RB1 is not involved in initial expansion of the preneoplastic clone. Instead, we found a set of contiguous genes that we term ""forerunner"" genes whose silencing is associated with the development of plaque-like field effects initiating carcinogenesis. Specifically, we identified five candidate forerunner genes (ITM2B, LPAR6, MLNR, CAB39L, and ARL11) mapping near RB1. Two of these genes, LPAR6 and CAB39L, are preferentially downregulated in the luminal and basal subtypes of bladder cancer, respectively. Their loss of function dysregulates urothelial differentiation, sensitizing the urothelium to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced cancers, which recapitulate the luminal and basal subtypes of human bladder cancer."	bladder
MR Evaluation of an Unusual Intruder of the Bladder: A Bladder Fibroid Case Report.	INTRODUCTION: Mesenchymal tumours of the bladder are benign but rare occurrences and represent approximately 1% of all bladder tumours. CASE REPORT: We report a case of a large bladder leiomyoma in an asymptomatic patient. A large pelvic mass was discovered incidentally on the bedside ultrasound scan during a review at the gynecology clinic. Intra-operatively, no mass was seen in the pelvis, and cystoscopy demonstrated an intravesical mass. It was further evaluated with cystoscopy. MR imaging demonstrated typical features of a bladder leiomyoma. Subsequently, the patient underwent partial cystectomy, and the mass was removed, which was histologically proven leiomyoma. CONCLUSION: Awareness of this rare clinical entity and identification of its typical radiological features on MR imaging can aid with accurate diagnosis and preclude unnecessary radical surgery.	bladder
Change in Tissue Microbiome and Related Human Beta Defensin Levels Induced by Antibiotic Use in Bladder Carcinoma.	It is now generally accepted that the success of antitumor therapy can be impaired by concurrent antibiotic therapy, the presence of certain bacteria, and elevated defensin levels around the tumor tissue. The aim of our current investigation was to identify the underlying changes in microbiome and defensin levels in the tumor tissue induced by different antibiotics, as well as the duration of this modification. The microbiome of the tumor tissues was significantly different from that of healthy volunteers. Comparing only the tumor samples, no significant difference was confirmed between the untreated group and the group treated with antibiotics more than 3 months earlier. However, antibiotic treatment within 3 months of analysis resulted in a significantly modified microbiome composition. Irrespective of whether Fosfomycin, Fluoroquinolone or Beta-lactam treatment was used, the abundance of Bacteroides decreased, and Staphylococcus abundance increased. Large amounts of the genus Acinetobacter were observed in the Fluoroquinolone-treated group. Regardless of the antibiotic treatment, hBD1 expression of the tumor cells consistently doubled. The increase in hBD2 and hBD3 expression was the highest in the Beta-lactam treated group. Apparently, antibiotic treatment within 3 months of sample analysis induced microbiome changes and defensin expression levels, depending on the identity of the applied antibiotic.	bladder
Efficacy of conduction hyperthermia in the treatment of non-muscle invasive bladder cancer: A systematic review.	INTRODUCTION: Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy. OBJECTIVE: To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC. MATERIAL AND METHODS: The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety. RESULTS: Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences. CONCLUSIONS: Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.	bladder
Detection of bladder cancer cells using quantitative interferometric label-free imaging flow cytometry.	Bladder cancer is one of the most common cancers with a high recurrence rate. Patients undergo mandatory yearly scrutinies, including cystoscopies, which makes bladder cancer highly distressing and costly. Here, we aim to develop a non-invasive, label-free method for the detection of bladder cancer cells in urine samples, which is based on interferometric imaging flow cytometry. Eight urothelial carcinoma and one normal urothelial cell lines, along with red and white blood cells, imaged quantitatively without staining by an interferometric phase microscopy module while flowing in a microfluidic chip, and classified by two machine-learning algorithms, based on deep-learning semantic segmentation convolutional neural network and extreme gradient boosting. Furthermore, urine samples obtained from bladder-cancer patients and healthy volunteers were imaged, and classified by the system. We achieved accuracy and area under the curve (AUC) of 99% and 97% for the cell lines on both machine-learning algorithms. For the real urine samples, the accuracy and AUC were 96% and 96% for the deep-learning algorithm and 95% and 93% for the gradient-boosting algorithm, respectively. By combining label-free interferometric imaging flow cytometry with high-end classification algorithms, we achieved high-performance differentiation between healthy and malignant cells. The proposed technique has the potential to supplant cystoscopy in the bladder cancer surveillance and diagnosis space.	bladder
Effective detection of BRAF(V595E) mutation in canine urothelial and prostate carcinomas using immunohistochemistry.	Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAF(V595E) mutation, akin to the BRAF(V600E) mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAF(V595E) and human BRAF(V600E) mutations, we hypothesized that immunohistochemistry (IHC) using a BRAF(V600E)-specific antibody could effectively identify the canine mutant BRAF(V595E) protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAF(V595E) was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAF(V595E) mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAF(V600)-specific IHC is a reliable and accurate method for detecting the mutant BRAF(V595E) protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost-efficient test for large-scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.	bladder
NECTIN4 Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.	PURPOSE: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS: We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS: NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION: NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.	bladder
USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway.	USP15, a pivotal member of the deubiquitinase family, plays a crucial role in orchestrating numerous vital biological processes, including the regulation of NF-κB signaling pathway and deubiquitination of proto-oncogenes. In various cancers, USP15 has been validated to exhibit up-regulated expression, impacting the initiation and progression of cancer. However, its precise mechanism in bladder cancer remains elusive. Our study shed light on the significant overexpression of USP15 in bladder cancer cells compared to normal bladder cells, correlating with a poorer prognosis for bladder cancer patients. Strikingly, attenuation of USP15 expression greatly attenuated the proliferation, migration, and invasion of bladder cancer cells. Moreover, upregulation of USP15 was found to drive cancer progression through the activation of the NF-κB signaling pathway. Notably, USP15 directly deubiquitinates BRCC3, heightening its expression level, and subsequent overexpression of BRCC3 counteracted the antitumoral efficacy of USP15 downregulation. Overall, our findings elucidated the carcinogenic effects of USP15 in bladder cancer, primarily mediated by the excessive activation of the NF-κB signaling pathway, thereby promoting tumor development. These results underscore the potential of USP15 as a promising therapeutic target for bladder cancer in the future.	bladder
Study on the Role and Mechanism of SLC3A2 in Tumor-Associated Macrophage Polarization and Bladder Cancer Cells Growth.	Background: Solute carrier family 3 member 2 (SLC3A2) is highly expressed in various types of cancers, including bladder cancer (BLCA). However, the role and mechanism of SLC3A2 in the onset and progression of BLCA are still unclear. Methods: The interfering plasmid for SLC3A2 was constructed and transfected into BLCA cells. Cell proliferation, invasion, and migration abilities were assessed to evaluate the impact of SLC3A2 silencing on BLCA cell growth. M1 and M2 macrophage polarization markers were detected to evaluate macrophage polarization. The levels of reactive oxygen species (ROS), lipid peroxidation, and Fe(2+), as well as the expression of ferroptosis-related proteins, were measured to assess the occurrence of ferroptosis. Ferroptosis inhibitors were used to verify the mechanism. Results: The experimental results showed that SLC3A2 was highly expressed in BLCA cell lines. The proliferation, invasion, and migration of BLCA cells were reduced after interfering with SLC3A2. Interference with SLC3A2 led to increase the expression of M1 macrophage markers and decreased the expression of M2 macrophage markers in M0 macrophages co-cultured with tumor cells. Additionally, interference with SLC3A2 led to increased levels of ROS, lipid peroxidation, and Fe(2+), downregulated the expression of solute carrier family 7 member11 (SLC7A11) and glutathione peroxidase 4 (GPX4), while upregulated the expression of acyl-coA synthetase long chain family member 4 (ACSL4) and transferrin receptor 1 (TFR1) in BLCA cells. However, the impact of SLC3A2 interference on cell proliferation and macrophage polarization was impeded by ferroptosis inhibitors. Conclusion: Interference with SLC3A2 inhibited the growth of BLCA cells and the polarization of tumor-associated macrophages by promoting ferroptosis in BLCA cells.	bladder
[Should we all switch to en-bloc resection of bladder tumours?].	In En-Bloc Resection of Bladder Tumours (ERBT), tumours are not removed in fragments, but are dissected in one layer and, if possible, extracted in one piece. This method represents a significant shift in the surgical management of non-muscle-invasive bladder tumours, providing multiple benefits over the traditional transurethral resection of the bladder (TUR-B). The histological analysis of ERBT specimens is more accurate, enhancing diagnostic precision. Additionally, the presence of detrusor muscle in ERBT specimens is more frequent, indicating a more complete removal of the tumours. Recent years have seen the consolidation of a robust evidence base emphasizing the advantages of ERBT. Notably, a multicentric, prospective randomized trial has recently revealed a significant reduction in recurrence rates at 12 months follow-up compared with TUR-B. Experienced endourologists should explore this technique, as it may soon become the standard of care. The technique's elegance and effectiveness make it too important to be ignored.	bladder
A Phase 2 Trial of Intravesical Gemcitabine and Docetaxel in the Treatment of Bacillus Calmette-Guérin‒Naïve Nonmuscle-Invasive Urothelial Carcinoma of the Bladder.	PURPOSE: Combination intravesical gemcitabine and docetaxel (GemDoce) has demonstrated efficacy as second-line therapy for patients with bacillus Calmette-Guérin (BCG)‒unresponsive nonmuscle-invasive urothelial carcinoma of the bladder (NMIBC). In the context of widespread BCG shortages, we performed a phase 2 prospective trial to assess GemDoce for BCG-naïve NMIBC. MATERIALS AND METHODS: This study is a prospective, single-arm, open-label phase 2 trial for patients with BCG-naïve high-risk NMIBC. Intravesical GemDoce was given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary end point was 3-month complete response, and key secondary end points included adverse events (AEs) and 12-month recurrence-free survival. RESULTS: Twenty-five patients were enrolled between August 2020 and August 2022 with median follow-up of 19.6 months. The pretreatment pathologic stages were high-grade (HG) T1 with carcinoma in situ (CIS; n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3). The 3-month complete response rate was 100% and recurrence-free survival at 12 months was 92%. Two patients with pretreatment HGT1 had HGT1 recurrences at 9 and 12 months. No patients progressed to T2 disease, underwent radical cystectomy, or had any radiographic evidence of progressive disease. Grade 1 AEs were common (23/25 patients) including hematuria, urinary frequency, urgency, and fatigue. Five patients (20%) experienced a grade 3 AE including hematuria and UTI. CONCLUSIONS: In this single-arm phase 2 trial, GemDoce was well tolerated with promising efficacy for patients with BCG-naïve high-risk NMIBC.	bladder